Near Infrared Microsensor for Continuous In-vivo Intraocular and Intracranial Pressure Monitoring.

Pressure monitoring in the nervous system is widely used to evaluate therapeutic interventions in patients with severe pathological elevated pressure in the brain (such as traumatic brain injuries (TBI) and hydrocephalus) and in the eye (e.g. glaucoma). Monitoring the pressure has been shown to reduce the number of deaths in TBI patients by 20% and number of blindness in glaucoma patients by 50%. Continuous, long-term in-vivo pressure monitoring, therefore is a necessity for planning interventional treatment for the patients in the risk. The clinical method for monitoring the pressure is not changes in past 40 years. Non-invasive tonometer for glaucoma patients are inaccurate and cannot be used for continuous monitoring. Current invasive clinical pressure monitoring practices often employ a catheter that records the pressure surgically inserted in the brain or in the eye. These catheter-based systems have been successful so far in accurately monitoring pressure but they are not appropriate for long-term monitoring as: (i) the patient is continuously connected to the non-portable monitoring unit, and (ii) the long-term placement of the catheter significantly increases the risk of infection. Motivated by the need for frequent, long-term pressure monitoring and the lack of commercially available fully implantable microsensors, we developed a novel class of MEMS-based, pressure technology, termed ‘Near infrared Fluorescent-based Optomechanical (NiFO)’ pressure sensing technology. NiFO technology is based on a fully implantable, powerless, optical microsensor (the NiFO sensor) that converts physiological pressure into a two-wavelength optical signal in the near infrared (NI) spectrum. NiFO microsensors were microfabricated using silicon bulk micromachining and were shown to operate at a physiologically relevant pressure range (0-100mmHg). They have a maximum error of less than 15 % throughout their dynamic range and they are extremely photostable. We adapted the microsensor design to measure intracranial pressure (ICP) and intraocular pressure (IOP) and we demonstrated their in-vivo operation for over a month in sheep. We envision that the proposed NiFO sensing technology will inaugurate a new era in the development of implantable, electronic and power-free miniaturized devices that can be used in a variety of biomedical pressure monitoring applications.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97943/1/mostafa_1.pd

Microfluidic Chips for In Vivo Imaging of Cellular Responses to Neural Injury in Drosophila Larvae

With powerful genetics and a translucent cuticle, the Drosophila larva is an ideal model system for live imaging studies of neuronal cell biology and function. Here, we present an easy-to-use approach for high resolution live imaging in Drosophila using microfluidic chips. Two different designs allow for non-invasive and chemical-free immobilization of 3rd instar larvae over short (up to 1 hour) and long (up to 10 hours) time periods. We utilized these ‘larva chips’ to characterize several sub-cellular responses to axotomy which occur over a range of time scales in intact, unanaesthetized animals. These include waves of calcium which are induced within seconds of axotomy, and the intracellular transport of vesicles whose rate and flux within axons changes dramatically within 3 hours of axotomy. Axonal transport halts throughout the entire distal stump, but increases in the proximal stump. These responses precede the degeneration of the distal stump and regenerative sprouting of the proximal stump, which is initiated after a 7 hour period of dormancy and is associated with a dramatic increase in F-actin dynamics. In addition to allowing for the study of axonal regeneration in vivo, the larva chips can be utilized for a wide variety of in vivo imaging applications in Drosophila

A Radial Flow Microfluidic Device for Ultra‐High‐Throughput Affinity‐Based Isolation of Circulating Tumor Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/1/smll201400719.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/2/smll201400719-sup-0001-S1.pd

A microfluidics-based method for measuring neuronal activity in Drosophila chemosensory neurons

Monitoring neuronal responses to defined sensory stimuli is a powerful and widely used approach for understanding sensory coding in the nervous system. However, providing precise, stereotypic and reproducible cues while concomitantly recording neuronal activity remains technically challenging. Here we describe the fabrication and use of a microfluidics system that allows precise temporally restricted stimulation of Drosophila chemosensory neurons with an array of different chemical cues. The system can easily be combined with genetically encoded calcium sensors, and it can measure neuronal activity at single-cell resolution in larval sense organs and in the proboscis or leg of the adult fly. We describe the design of the master mold, the production of the microfluidic chip and live imaging using the calcium sensor GCaMP, expressed in distinct types of Drosophila chemosensory neurons. Fabrication of the master mold and microfluidic chips requires basic skills in photolithography and takes ~2 weeks; the same devices can be used repeatedly over several months. Flies can be prepared for measurements in minutes and imaged for up to 1 h

Engineering brain activity patterns by neuromodulator polytherapy for treatment of disorders

Conventional drug screens and treatments often ignore the underlying complexity of brain network dysfunctions, resulting in suboptimal outcomes. Here we ask whether we can correct abnormal functional connectivity of the entire brain by identifying and combining multiple neuromodulators that perturb connectivity in complementary ways. Our approach avoids the combinatorial complexity of screening all drug combinations. We develop a high-speed platform capable of imaging more than 15000 neurons in 50ms to map the entire brain functional connectivity in large numbers of vertebrates under many conditions. Screening a panel of drugs in a zebrafish model of human Dravet syndrome, we show that even drugs with related mechanisms of action can modulate functional connectivity in significantly different ways. By clustering connectivity fingerprints, we algorithmically select small subsets of complementary drugs and rapidly identify combinations that are significantly more effective at correcting abnormal networks and reducing spontaneous seizures than monotherapies, while minimizing behavioral side effects. Even at low concentrations, our polytherapy performs superior to individual drugs even at highest tolerated concentrations

An Optofluidic Lens Array Microchip for High Resolution Stereo Microscopy

We report the development of an add-on, chip-based, optical module—termed the Microfluidic-based Oil-immersion Lenses (μOIL) chip—which transforms any stereo microscope into a high-resolution, large field of view imaging platform. The μOIL chip consists of an array of ball mini-lenses that are assembled onto a microfluidic silicon chip. The mini-lenses are made out of high refractive index material (sapphire) and they are half immersed in oil. Those two key features enable submicron resolution and a maximum numerical aperture of ~1.2. The μOIL chip is reusable and easy to operate as it can be placed directly on top of any biological sample. It improves the resolution of a stereo microscope by an order of magnitude without compromising the field of view; therefore, we believe it could become a versatile tool for use in various research studies and clinical applications

Engineering brain activity patterns by neuromodulator polytherapy for treatment of disorders

Conventional drug screens and treatments often ignore the underlying complexity of brain network dysfunctions, resulting in suboptimal outcomes. Here we ask whether we can correct abnormal functional connectivity of the entire brain by identifying and combining multiple neuromodulators that perturb connectivity in complementary ways. Our approach avoids the combinatorial complexity of screening all drug combinations. We develop a high-speed platform capable of imaging more than 15000 neurons in 50ms to map the entire brain functional connectivity in large numbers of vertebrates under many conditions. Screening a panel of drugs in a zebrafish model of human Dravet syndrome, we show that even drugs with related mechanisms of action can modulate functional connectivity in significantly different ways. By clustering connectivity fingerprints, we algorithmically select small subsets of complementary drugs and rapidly identify combinations that are significantly more effective at correcting abnormal networks and reducing spontaneous seizures than monotherapies, while minimizing behavioral side effects. Even at low concentrations, our polytherapy performs superior to individual drugs even at highest tolerated concentrations.ISSN:2041-172